Role of Environmental Factors in the Pharmacokinetics of Drugs: Considerations with Respect to Animal Models, P-450 Enzymes, and Probe Drugs

Human beings live in changing environments in which some factors change very rapidly and others more slowly. Organisms must adapt themselves to these changes if they are to survive and reproduce. A specific aspect of the adaptation is the mechanism by which organisms try to maintain homeostasis in respect to the chemical environment. Organisms are endowed with the enzyme machinery which disposes of chemicals that have entered the body. These enzymes are called drug- or xenobiotic-metabolizing enzymes and they have been dealt with in numerous monographs, review articles, and symposia during the past 30 years or so (see, e.g., Jenner and Testa 1980; Ortiz De Montellano 1986; Benford et al. 1987; Alvares and Pratt 1990; Tukey and Johnson 1990).